A One-Pot Multicomponent 1,3-Dipolar Cycloaddition Strategy: Combinatorial Synthesis of Dihydrothiophenone-Engrafted Dispiro Hybrid Heterocycles

Rani, Mani Anusha; Kumar, Sundaravel Vivek; Malathi, Karuppiah; Muthu, Muthumani; Almansour, Abdulrahman I.; Kumar, Raju Suresh; Kumar, Raju Ranjith

doi:10.1021/acscombsci.6b00186

Cited by 29 publications

(6 citation statements)

References 49 publications

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“…Some succinimide derivatives, for instance, are used as antimycobacterial for treatment of Mycobacteria infections, [44,45] to suppress cancer cell proliferation [46] and act as anticonvulsant agents [47,48] (Figure 2). Among the typical synthetic strategies leading to these spiroheterocyclic scaffolds, the multicomponent 1,3-dipolar cycloaddition of electron-deficient exocyclic alkenes with azomethine ylides, generated in situ from α-aminoacids and 1,2-diketones, is the most widely reported one [35][36][37][38][39][40][41]. Its process simplicity combined with mild reaction conditions and atomic economy addresses several aspects required for combinatorial chemistry.…”

Section: Introductionmentioning

confidence: 99%

Three-Component Access to Functionalized Spiropyrrolidine Heterocyclic Scaffolds and Their Cholinesterase Inhibitory Activity

et al. 2020

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A novel one-pot [3+2]-cycloaddition reaction of (E)-3-arylidene-1-phenyl-succinimides, cyclic 1,2-diketones (isatin, 5-chloro-isatin and acenaphtenequinone), and diverse α-aminoacids such as 2-phenylglycine or sarcosine is reported. The reaction provides succinimide-substituted dispiropyrrolidine derivatives with high regio- and diastereoselectivities under mild reaction conditions. The stereochemistry of these N-heterocycles has been confirmed by four X-ray diffraction studies. Several synthetized compounds show higher inhibition on acetylcholinesterase (AChE) than butyrylcholinesterase (BChE). Of the 17 synthesized compounds tested, five exhibit good AChE inhibition with IC50 of 11.42 to 22.21 µM. A molecular docking study has also been undertaken for compound 4n possessing the most potent AChE inhibitory activity, disclosing its binding to the peripheral anionic site of AChE enzymes.

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Section: Introductionmentioning

confidence: 99%

Three-Component Access to Functionalized Spiropyrrolidine Heterocyclic Scaffolds and Their Cholinesterase Inhibitory Activity

et al. 2020

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“…Isatin-derived azomethine ylides were recognized as typical dipoles and generally generated in situ by decarboxylative condensation of α -amino acids with isatins, which then react with dipolarophiles [ 31 ]. Significantly, diverse dipolarophiles have proven highly fruitful, including electron-deficient alkenes (activated by nitro [ 32 , 33 , 34 , 35 , 36 ], carbonyl [ 37 , 38 , 39 , 40 ], or other electron-withdrawing groups [ 41 , 42 , 43 ]), alkynes [ 44 , 45 , 46 ], arylacetylenes [ 47 ], allenes [ 48 ], N -heteroenes [ 49 , 50 ], and strained cyclopropenes [ 51 ]. However, previously reported methods mainly focused on the traditional ‘single target’ approach, and thus, only one type of spirooxindole skeleton can be prepared via the 1,3-dipolar cycloaddition of isatin-derived azomethine ylides to monogroup-activated dipolarophiles.…”

Section: Introductionmentioning

confidence: 99%

Dipolarophile-Controlled Regioselective 1,3-Dipolar Cycloaddition: A Switchable Divergent Access to Functionalized N-Fused Pyrrolidinyl Spirooxindoles

Wang

Liang

Yan

et al. 2023

IJMS

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N-fused pyrrolidinyl spirooxindole belongs to a class of privileged heterocyclic scaffolds and is prevalent in natural alkaloids and synthetic pharmaceutical molecules. To realize the switchable synthesis of divergent N-fused pyrrolidinyl spirooxindoles for further biological activity evaluation via a substrate-controlled strategy, a chemically sustainable, catalysis-free, and dipolarophile-controlled three-component 1,3-dipolar cycloaddition of isatin-derived azomethine ylides with diverse dipolarophiles is described in this work. A total of 40 functionalized N-fused pyrrolidinyl spirooxindoles were synthesized in 76–95% yields with excellent diastereoselectivities (up to >99:1 dr). The scaffolds of these products can be well-controlled by employing different 1,4-enedione derivatives as dipolarophiles in EtOH at room temperature. This study provides an efficient strategy to afford a spectrum of natural-like and potentially bioactive N-fused pyrrolidinyl spirooxindoles.

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“…Multicomponent reactions (MCRs) offer a chance for the combination of three or more flexible and straightforward building blocks in a one-pot operation, constructing complex structures by the continuous formation of two or more bonds, according to the domino principle. − Environmentally friendly processes via decreasing the waste production, number of synthetic steps, and energy depletion are among the benefits of MCRs. − …”

Section: Introductionmentioning

confidence: 99%

Rapid Construction of Substituted Dihydrothiophene Ureidoformamides at Room Temperature Using Diisopropyl Ethyl Ammonium Acetate: A Green Perspective

et al. 2020

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An economic, sustainable, and straightforward environmentally friendly synthesis of highly diversified polyfunctional dihydrothiophenes is successfully achieved via diisopropyl ethyl ammonium acetate as a room-temperature ionic liquid. Multicomponent synthesis contains domino processes; the benefit of this present protocol is highlighted by its readily available starting materials, superior functional group tolerance, purity of synthesized compounds was checked by high-performance liquid chromatography results in up to 99.7% purity for the synthesized compounds, reaction mass efficiency, effective mass yield, and excellent atom economy. In addition, a series of 2-(N-carbamoyl acetamide)-substituted 2,3-dihydrothiophene analogs were synthesized, and selected samples were chosen for testing their in vitro antibacterial and antifungal activities. Furthermore, a molecular docking study against sterol 14α-demethylase could provide valuable insight into the mechanism of antifungal action providing an opportunity for structure-based lead optimization.

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A One-Pot Multicomponent 1,3-Dipolar Cycloaddition Strategy: Combinatorial Synthesis of Dihydrothiophenone-Engrafted Dispiro Hybrid Heterocycles

Abstract: The combinatorial syntheses of a library of novel dihydrothiophenone-engrafted dispiro oxindole/indenoquinoxaline-pyrrolidine/pyrrolothiazole/indolizine hybrid heterocycles have been realized through a chemo-, regio-, and stereoselective multicomponent 1,3-dipolar cycloaddition strategy.

Cited by 29 publications

References 49 publications

Three-Component Access to Functionalized Spiropyrrolidine Heterocyclic Scaffolds and Their Cholinesterase Inhibitory Activity

Three-Component Access to Functionalized Spiropyrrolidine Heterocyclic Scaffolds and Their Cholinesterase Inhibitory Activity

Dipolarophile-Controlled Regioselective 1,3-Dipolar Cycloaddition: A Switchable Divergent Access to Functionalized N-Fused Pyrrolidinyl Spirooxindoles

Rapid Construction of Substituted Dihydrothiophene Ureidoformamides at Room Temperature Using Diisopropyl Ethyl Ammonium Acetate: A Green Perspective

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